Ultrastructural fingerprints of avian influenza A (H7N9) virus in infected human lung cells

Terrier, B.; Carron, Coralie; Cartet, Gaëlle; Traversier, Aurélien; Julien, Thomas; Valette, Martine; Lina, Bruno; Moulés, Vincent; Rosa‐Calatrava, Manuel

doi:10.1016/j.virol.2014.03.013

Cited by 9 publications

(17 citation statements)

References 13 publications

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“…Several investigations, including ours, have revealed that IAV induce a strong remodeling of nuclear architecture with marked modifications of the nucleoli ultrastructure and compartments 3 17 18 19 20 . The nucleolus, known as the site of ribosome biogenesis, is also a sensor of cellular stresses and is involved in several cellular pathways, such as cell-cycle regulation or apoptosis 21 22 23 .…”

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confidence: 66%

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Nucleolin interacts with influenza A nucleoprotein and contributes to viral ribonucleoprotein complexes nuclear trafficking and efficient influenza viral replication

Terrier¹,

Carron²,

Chassey³

et al. 2016

Sci Rep

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Influenza viruses replicate their single-stranded RNA genomes in the nucleus of infected cells and these replicated genomes (vRNPs) are then exported from the nucleus to the cytoplasm and plasma membrane before budding. To achieve this export, influenza viruses hijack the host cell export machinery. However, the complete mechanisms underlying this hijacking remain not fully understood. We have previously shown that influenza viruses induce a marked alteration of the nucleus during the time-course of infection and notably in the nucleolar compartment. In this study, we discovered that a major nucleolar component, called nucleolin, is required for an efficient export of vRNPs and viral replication. We have notably shown that nucleolin interacts with the viral nucleoprotein (NP) that mainly constitutes vRNPs. Our results suggest that this interaction could allow vRNPs to “catch” the host cell export machinery, a necessary step for viral replication.

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confidence: 66%

“…In the context of IAV, their interplay with nucleolus and selective interactions with several nucleolar components appears to be decisive in the outcome of infection 17 20 . Ozawa and colleagues demonstrated that dynamic nucleolar localization of NP is functionally significant by contributing to efficient viral replication and transcription 27 .…”

mentioning

confidence: 99%

Nucleolin interacts with influenza A nucleoprotein and contributes to viral ribonucleoprotein complexes nuclear trafficking and efficient influenza viral replication

Terrier¹,

Carron²,

Chassey³

et al. 2016

Sci Rep

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“…L'émergence de nouveaux variants viraux par dérive antigénique (comme observé en Une stratégie innovante d'identification de nouveaux antiviraux ciblant la cellule infectée Transcriptome Le succès de telles stratégies repose en grande partie sur notre capacité à caractériser davantage la biologie cellulaire de ces virus respiratoires et leurs interactions moléculaires et fonctionnelles avec leur hôte. Ces dernières années, de nouvelles approches de biologie cellulaire de l'infection [38][39][40][41][42], et en particulier le développement de la biologie des systèmes, ont considérablement enrichi les connaissances concernant les interactions complexes et multiples entre ces virus et la « machinerie » cellulaire. Parmi elles, les études de la réponse transcriptomique de l'hôte ont permis de mettre en évidence les voies de signalisation sollicitées et/ou détournées lors de l'infection [43,44].…”

Section: Limites De La Vaccination Et Des Traitements Antivirauxunclassified

La modulation de la signature transcriptomique de l’hôte infecté : une nouvelle stratégie thérapeutique dans les viroses graves ? Exemple de la grippe

et al. 2016

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Ces dernières décennies ont été marquées par l'émergence ou la réémergence de virus responsables d'épidémies ou de pandémies plus ou moins sévères. Les stratégies préventives sont prises à défaut, et l'arsenal antiviral curatif est limité d'autant plus que les résistances virales peuvent apparaître rapidement. Par ailleurs, le développement de nouvelles molécules nécessite un délai incompatible avec la réponse rapide nécessaire lors d'une épidémie d'envergure ou d'une pandémie. C'est la raison pour laquelle de nouvelles approches thérapeutiques sont nécessaires. Un concept novateur est le repositionnement de molécules déjà sur le marché en exploitant leur capacité à inverser la réponse transcriptomique cellulaire de l'hôte infecté. En identifiant des molécules qui visent l'hôte et non le virus, cette stratégie permet d'avoir un large spectre d'action et d'être potentiellement actif sur de nouveaux variants. La mise en place de cette stratégie nécessite de caractériser les réponses cellulaires spécifiques de l'infection virale d'intérêt, de cribler in silico des molécules candidates, de les tester sur modèles cellulaires et animaux, avant d'envisager des essais cliniques chez l'homme. Nous présenterons cette démarche en prenant pour exemple l'infection grippale. Mots clés Viroses · Grippe · Transcriptome · Repositionnement de médicamentsAbstract During the last decades, emergence and reemergence of viruses were responsible for epidemic and pandemic infectious diseases, with variable degrees of severity. Current preventive strategies are not sufficient at all, and available therapeutic drugs are very limited. Indeed, genetic variations of viruses can impair the efficacy of antiviral compounds by the apparition of resistance. Moreover, current delay needed for de novo development of drugs does not allow a rapid response in case of important epidemic or pandemic events. In this context, new therapeutic approaches are necessary. An innovative concept is to repurpose already marketed compounds that can reverse the host cellular transcriptomic response to the infection. By targeting the host, these molecules exhibit a broad-spectrum activity and are potentially effective even against new emergent strains. This

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Section: Introductionmentioning

confidence: 99%

“…Ultrastructural changes in the human lung cells infected with H7N9 virus have been studied by electron microscopy [7]. One characteristic of H7N9 viral infection was the formation of numerous tubular structures within the nucleus and the cytoplasm, which have previously been observed for some influenza A viruses including the 2009 pandemic (H1N1) virus [7]. In general, the envelope of the influenza A virus is made of a lipid bilayer derived from the host cell and contains glycoprotein spikes of two types, hemagglutinin (HA), a ~14 nm long trimer, and neuraminidase (NA), a ~16 nm long tetramer [8,9] (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Recombinant Hemagglutinin and Virus-Like Particle Vaccines for H7N9 Influenza virus

Li¹,

Pushko

Tretyakova

2015

J Vaccines Vaccin

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Cases of H7N9 human infection were caused by a novel, avian-origin H7N9 influenza A virus that emerged in eastern China in 2013. Clusters of human disease were identified in many cities in China, with mortality rates approaching 30%. Pandemic concerns were raised, as historically, influenza pandemics were caused by introduction of novel influenza A viruses into immunologically naïve human population. Currently, there are no approved human vaccines for H7N9 viruses. Recombinant protein vaccine approaches have advantages in safety and manufacturing. In this review, we focused on evaluation of the expression of recombinant hemagglutinin (rHA) proteins as candidate vaccines for H7N9 influenza, with the emphasis on the role of oligomeric and particulate structures in immunogenicity and protection. Challenges in preparation of broadly protective influenza vaccines are discussed, and examples of broadly protective vaccines are presented including rHA stem epitope vaccines, as well as recently introduced experimental multi-HA VLP vaccines.

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Ultrastructural fingerprints of avian influenza A (H7N9) virus in infected human lung cells

Cited by 9 publications

References 13 publications

Nucleolin interacts with influenza A nucleoprotein and contributes to viral ribonucleoprotein complexes nuclear trafficking and efficient influenza viral replication

Nucleolin interacts with influenza A nucleoprotein and contributes to viral ribonucleoprotein complexes nuclear trafficking and efficient influenza viral replication

La modulation de la signature transcriptomique de l’hôte infecté : une nouvelle stratégie thérapeutique dans les viroses graves ? Exemple de la grippe

Recombinant Hemagglutinin and Virus-Like Particle Vaccines for H7N9 Influenza virus

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